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Biomedical subjects

D Turton

Publications and source records attributed to D Turton.

11 recordsLinked to original sources

Anemia: a cause of intolerance to thyroxine sodium.

Usual causes of intolerance to thyroxine sodium include coronary artery disease, advanced age, untreated adrenal insufficiency, and severe hypothyroidism. We describe 4 patients with iron deficiency anemia and primary hypothyroidism. After treatment with thyroxine sodium, these patients developed palpitations and feelings of restlessness, which necessitated discontinuation of the thyroid hormone. After the anemia was treated with ferrous sulfate for 4 to 7 weeks, they were able to tolerate thyroxine sodium therapy. Iron deficiency anemia coexisting with primary hypothyroidism results in a hyperadrenergic state. In such patients, we postulate that thyroid hormone administration causes palpitations, nervousness, and feelings of restlessness. Correction of any existing pronounced anemia in hypothyroid patients who are intolerant to thyroxine sodium therapy may result in tolerance to this agent.

Adult↗

Measurement of human cerebral monoamine oxidase type B (MAO-B) activity with positron emission tomography (PET): a dose ranging study with the reversible inhibitor Ro 19-6327.

Eight normal subjects (3 females and 5 males) were studied using intravenous L-[11C] deprenyl and positron emission tomography. In a single blind study one subject received tracer alone, one subject received an oral pre-dose of 20 mg of L-deprenyl and 6 subjects received oral pre-doses of 10 to 50 mg of a novel reversible MAO-B inhibitor (Ro 19-6327). Dynamic PET scans beginning 12 h after the oral dose were collected over 90 min and arterial blood was continuously sampled. Data analysis was modelled for two tissue compartments and using an iterative curve fitting technique the value of the rate constant for irreversible binding of L-[11C] deprenyl to MAO-B (k3) in whole brain was obtained for each subject. The dose response curves obtained indicated that a dose of at least 0.48 mg.kg-1 of Ro 19-6327 was necessary for greater than 90% decrease in whole brain k3. Inhibition of MAO-B in platelets isolated from blood samples taken at the time of scanning correlated strongly with decrease in whole brain k3 (r = 0.949). The results indicate that PET can be used to determine the dose of Ro 19-6327 necessary to inhibit greater than 90% of brain MAO-B. This technique is an attractive alternative to traditional large scale patient-based dose-finding studies. Moreover it is shown that inhibition of platelet MAO-B can be used as a marker for central MAO-B inhibition with Ro 19-6327.

Aged↗

Measurement of cerebral monoamine oxidase B activity using L-[11C]deprenyl and dynamic positron emission tomography.

A tracer kinetic procedure was developed for the measurement of monoamine oxidase type B (MAO-B) activity using L-[11C]deprenyl and positron emission tomography (PET). The kinetic model consisted of two tissue compartments with irreversible binding to the second compartment (three rate constants). In addition, a blood volume component was included. Special attention was given to the accurate measurement of the plasma and whole blood input functions. The method was applied to the measurement of the dose-response curve of a reversible MAO-B inhibitor (Ro 19-6327). From the results, it followed that the rate constant for irreversible binding (k3) appeared to be a better index of MAO-B activity than the net influx constant Ki. Furthermore, regional analysis demonstrated that Ki, but not k3, was flow dependent. This implies that full kinetic analysis is required for an accurate assessment of MAO-B activity.

Aged↗

The routine analysis of some specific isomers of polychlorinated biphenyl congeners in human milk.

A mixture of 14 polychlorinated biphenyl (PCB) isomers of various congeners, representing approximately 70% of all human milk PCBs reported in the literature, was made up to identify and approximate their residues in human milk. Individual isomer levels varied from 5 to 103 nanograms per gram of milkfat with the 2,2',4,4',5,5'-hexachlorobiphenyl isomer as the major PCB contaminant of human milk. PCB isomer numbers 74, 118, 153, 138 and 180 made up approximately 75% of all PCBs as measured by this mixture. There was close agreement of total PCB isomer content in breast milk between electron capture gas chromatography and gas chromatographic mass spectrometry determinations. A major interference was encountered however for PCB isomer no. 52, whose residue level in the breast milk was approximately 3 X higher by gas liquid chromatography than by mass spectrometry.

Canada↗

Environmental contaminants in human fat: a comparison between accidental and nonaccidental causes of death.

A total of 29 human adipose tissue samples from autopsies of nonaccidental death victims from across Canada were analyzed for polychlorinated biphenyls and organochlorine pesticides. The residue levels of nonaccidental death victims were compared to those obtained earlier for samples of accidental death victims, collected during the same time period. A statistically significant difference was observed for hexachloro-1,3-butadiene (P less than 0.005) between the two sampling procedures. No statistically significant differences were found for other residues, although residue levels of hexachlorobenzene and p,p'-DDE were numerically higher in nonaccident than accident victims. Samples of nonaccidental deaths were subdivided into "sudden" and "other" death groups. Residue levels according to sex were statistically not related to the cause of death, although numerically the average p,p'-DDE level in male adipose tissue was higher in the "other" than "sudden" death group. The average p,p'-DDT levels in female adipose tissue of nonaccident victims were numerically at least twice those of accident victims, but were not statistically different.

Accidents↗

Validation of quantitation of regional myocardial blood flow in vivo with 11C-labeled human albumin microspheres and positron emission tomography.

Use of radiolabeled microspheres is a standard method to measure regional myocardial perfusion in animals. Human albumin microspheres have been given safely to patients, but positron-emitting 68Ga-labeled human albumin microspheres are characterized by an unstable radiolabel. A new labeling procedure that covalently binds 11C (t1/2 = 20.3 min) to human albumin microspheres via 11CH3I was developed. Seven open-chest and two closed-chest dogs were studied. Reference and 11C-labeled human albumin microspheres (2 to 25 mCi) were both injected into the left atrium. Positron tomographic images were obtained of the myocardial distribution of the 11C-labeled microspheres. Timed arterial withdrawal was used for both reference gamma-labeled microspheres and 11C-labeled human albumin microspheres. Myocardial tissue samples matched to tomographic slices were well-counted for calculation of reference values of regional myocardial perfusion. Serial venous blood samples for residual 11C activity of 30 and 60 min after injection were less than 1% of the myocardial 11C concentration demonstrating a stable 11C bond to the human albumin microspheres. Regional myocardial perfusion calculated by this technique correlated well with values obtained with reference microspheres (r = .97) over a range of 0.2 to 3.5 ml/min/g. Correction for wall thickness improved the slope of the regression equation from y = 0.71 x -0.03 to y = 0.88 X -0.05. Thus, 11C human albumin microspheres are stable radiochemically and can be used as a quantitative measure of regional myocardial perfusion.

Animals↗

Levels and trends of chlorinated hydrocarbon contaminants in the breast milk of Canadian women.

A total of 210 breast milk samples from 5 different regions across Canada were analyzed for polychlorinated biphenyls (PCBs), hexachloro-1,3-butadiene, ten chlorinated benzenes, two chlorinated naphthalenes, Mirex, photomirex, alpha, beta and gamma hexachlorocyclohexane, alpha and gamma chlordane, oxychlordane, trans-nonachlor, p,p'-DDT and some analogs, heptachlor epoxide, dieldrin and octachlorostyrene. There was no evidence for the presence of hexachloro-1,3-butadiene, Mirex, octachlorostyrene, chlorinated naphthalenes or tetrachlorobenzenes in the breast milk. Residues of other compounds were found in all samples, except 1,2-dichlorobenzene, gamma hexachlorocyclohexane, alpha and gamma chlordane and p,p'-TDE, which were less frequently observed, while o,p'-DDT was only found in approximately one quarter of all samples. Since 1967, a steady decline in heptachlor epoxide, dieldrin and p,p'-DDT and related residues is apparent. At the same time however, there is an apparent increase in PCB residue levels since 1970. This apparent increase should be viewed with some caution, since much of this increase might be attributed to better sampling and analytical techniques. Residue levels of breast milk in Canada were similar to those found in other industrial nations. Regional differences in residue levels appeared to be minimal.

Canada↗